Phosphodiesterase (PDE) is an enzyme that catalyzes the hydrolysis of cyclic AMP and/or cyclic GMP into 5-AMP and 5-GMP, respectively, in cells, and thus this enzyme is important in the cellular regulation at the level of cAMP or cGMP. So far, 11 families of PDEs have been known (Nature, 674-682(2002)). Of the PDEs, PDE 5 is an enzyme that decomposes cGMP to generate 5′-GMP, and thus it has been reported that the inhibition of PDE 5 maintains the concentration of cGMP to make an erection last (Boolel, M. et al., Br. J. of Urology, 78, 257-261(1996)). Therefore, a PDE 5 inhibitor is used as an erectile dysfunction medication.
Many compounds are known as a PDE 5 inhibitor. Viagra™ (generic name: sildenafil; WO 94/28902) was approved as the first male erectile dysfunction medicine by the U.S. FDA, and Cialis™ (generic name: tadalafil; WO 95/19978) and Levitra™ (generic name: vardenafil; Bioorganic & Medicinal Chemistry Letters) were permitted. Embix™ (generic name: mirodenafil; KR0358083) is also known as a PDE 5 inhibitor. The above medications are known to show an excellent treatment effect and thus improve the sexual function in approximately 70% of patients. As other medicinal uses of the PDE 5 inhibitor, the treatment effects of portal hypertension, liver-kidney syndrome, and liver-lung syndrome are known (Korean Patent Publication No. 10-2012-0024807), and the improvement effect of a reproductive capacity of mammals has also been reported (Korean Patent Publication No. 10-2002-0031062).
In addition, it has been reported that sildenafil and vardenafil as PDE 5 inhibitors induce caspase-dependent apoptosis of B-chronic lymphocytic leukemia cells (Marika Sarfati et al., BLOOD, VOLUME 101, NUMBER 1 (2003)).
Throughout this application, various patents and publications are referenced and citations are provided in parentheses. The disclosure of these patents and publications in their entities are hereby incorporated by references into this application in order to more fully describe this invention and the state of the art to which this invention pertains.